1-ethoxy-3-fluorobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.6M Butyl lithium in hexane (24 ml, 38.4 mmol) was added slowly (0.5 h) to a solution of 1-ethoxy-3-fluorobenzene (5.0 g, 35.7 mmol) in 100 ml of dry THF at -65° C. under nitrogen. The solution was stirred at -65° C. for 25 min. DMF (5.22 g, 71.4 mmol) was added dropwise to the solution. The mixture was allowed to warm to room temperature. 300 ml of ice was poured to this mixture and it was extracted with diethyl ether. Diethyl ether was washed with brine, dried over Na2SO4 and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100) to give 2-ethoxy-6-fluorobenzaldehyde. to warm to room temperature was extracted with diethyl ether Diethyl ether was washed with brine dried over Na2SO4 evaporated The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluorophenol (20.0 g, 178.4 mmol), ethyl iodide (83.5 g, 535.2 mmol) and K2CO3 (49.3 g, 356.8 mmol) in 250 ml of acetone were stirred at 50° C. overnight. The mixture was filtered and evaporated to give 1-ethoxy-3-fluorobenzene. The mixture was filtered evaporated

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.6M Butyl lithium in hexane (24 ml, 38.4 mmol) was added slowly (0.5 h) to a solution of 1-ethoxy-3-fluorobenzene (5.0 g, 35.7 mmol) in 100 ml of dry THF at -65° C. under nitrogen. The solution was stirred at -65° C. for 25 min. DMF (5.22 g, 71.4 mmol) was added dropwise to the solution. The mixture was allowed to warm to room temperature. 300 ml of ice was poured to this mixture and it was extracted with diethyl ether. Diethyl ether was washed with brine, dried over Na2SO4 and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100) to give 2-ethoxy-6-fluorobenzaldehyde. to warm to room temperature was extracted with diethyl ether Diethyl ether was washed with brine dried over Na2SO4 evaporated The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100)

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.6M Butyl lithium in hexane (24 ml, 38.4 mmol) was added slowly (0.5 h) to a solution of 1-ethoxy-3-fluorobenzene (5.0 g, 35.7 mmol) in 100 ml of dry THF at -65° C. under nitrogen. The solution was stirred at -65° C. for 25 min. DMF (5.22 g, 71.4 mmol) was added dropwise to the solution. The mixture was allowed to warm to room temperature. 300 ml of ice was poured to this mixture and it was extracted with diethyl ether. Diethyl ether was washed with brine, dried over Na2SO4 and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100) to give 2-ethoxy-6-fluorobenzaldehyde. to warm to room temperature was extracted with diethyl ether Diethyl ether was washed with brine dried over Na2SO4 evaporated The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluorophenol (20.0 g, 178.4 mmol), ethyl iodide (83.5 g, 535.2 mmol) and K2CO3 (49.3 g, 356.8 mmol) in 250 ml of acetone were stirred at 50° C. overnight. The mixture was filtered and evaporated to give 1-ethoxy-3-fluorobenzene. The mixture was filtered evaporated

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.6M Butyl lithium in hexane (24 ml, 38.4 mmol) was added slowly (0.5 h) to a solution of 1-ethoxy-3-fluorobenzene (5.0 g, 35.7 mmol) in 100 ml of dry THF at -65° C. under nitrogen. The solution was stirred at -65° C. for 25 min. DMF (5.22 g, 71.4 mmol) was added dropwise to the solution. The mixture was allowed to warm to room temperature. 300 ml of ice was poured to this mixture and it was extracted with diethyl ether. Diethyl ether was washed with brine, dried over Na2SO4 and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100) to give 2-ethoxy-6-fluorobenzaldehyde. to warm to room temperature was extracted with diethyl ether Diethyl ether was washed with brine dried over Na2SO4 evaporated The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluorophenol (20.0 g, 178.4 mmol), ethyl iodide (83.5 g, 535.2 mmol) and K2CO3 (49.3 g, 356.8 mmol) in 250 ml of acetone were stirred at 50° C. overnight. The mixture was filtered and evaporated to give 1-ethoxy-3-fluorobenzene. The mixture was filtered evaporated

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(3-Ethoxy-phenyl)-2-methyl-propionitrile was prepared using a procedure adapted from literature (Organic Syntheses, Vol. 79, pp. 209-215). To a solution of 1-ethoxy-3-fluoro benzene (3.0 g, 19.4 mmol) in 25 mL of toluene was added solid potassium bis(trimethylsilyl)amide (5.84 g, 29.2 mmol, 1.5 eq) followed by isobutyronitrile (7.08 mL, 77.8 mmol, 4 eq). The reaction mixture was stirred at 100° C. for 12 hr. It was diluted with 75 mL of ethyl acetate and 75 mL of 1N aqueous hydrochloric acid. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water (1×50 mL), brine (1×50 mL), and dried over anhydrous magnesium sulfate. The solids were filtered off, and the filtrate was concentrated in vacuo. The residue was dissolved in 5 mL of methylene chloride and applied to a 40 g silica gel cartridge. The product was eluted using a gradient of ethyl acetate in hexanes to yield 2.96 g (15.6 mmol, 80%) of pure 2-(3-ethoxy-phenyl)-2-methyl-propionitrile. LR-MS: 190.12 [(M+H)+] 2-(3-Ethoxy-phenyl)-2-methyl-propionitrile was prepared The layers were separated the aqueous layer was extracted with ethyl acetate The combined organic layers were washed with water (1×50 mL), brine (1×50 mL) dried over anhydrous magnesium sulfate The solids were filtered off the filtrate was concentrated in vacuo The residue was dissolved in 5 mL of methylene chloride The product was eluted

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-fluoro-phenol and ethyl iodide were reacted to form 3-fluoro-ethoxy benzene with a refractive index of nD25 =1.4823 which was reacted with nitric acid to obtain 2-ethoxy-4-fluoronitro benzene with a melting point of 28°~30° C. which was reacted to obtain 0-(4-nitro-3-ethoxy-phenyl)-hydroxylamine melting at 97°~98° C.

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.6M Butyl lithium in hexane (24 ml, 38.4 mmol) was added slowly (0.5 h) to a solution of 1-ethoxy-3-fluorobenzene (5.0 g, 35.7 mmol) in 100 ml of dry THF at -65° C. under nitrogen. The solution was stirred at -65° C. for 25 min. DMF (5.22 g, 71.4 mmol) was added dropwise to the solution. The mixture was allowed to warm to room temperature. 300 ml of ice was poured to this mixture and it was extracted with diethyl ether. Diethyl ether was washed with brine, dried over Na2SO4 and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100) to give 2-ethoxy-6-fluorobenzaldehyde. to warm to room temperature was extracted with diethyl ether Diethyl ether was washed with brine dried over Na2SO4 evaporated The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100)